Therapeutic potential of convalescent plasma and hyperimmune immunoglobulins against SARS-CoV-2 BQ.1, BQ.1.1, and XBB variants
Authors: Lorenza Bellusci, Hana Golding, Surender Khurana
Journal: Journal of Clinical Investigation (2023)

To the Editor: Convalescent plasma (CP) and hyperimmune intravenous immunoglobulins (IVIGs) are routinely used to treat patients with COVID-19.SARS-CoV-2 Omicron variants continue to evolve, generating multiple sublineages with increased transmissibility and antibody-escape mutations (1, 2).Several Omicron lineages that are currently circulating (BA.4,BA.5, BA.2.75, BA.2.75.2, BQ.1, BQ.1.1,and recombinant XBB) contain many mutations in spike protein (Supplemental Table 1; supplemental material available online with this article; https://doi.org/10.1172/JCI168583DS1),resulting in resistance to most therapeutic monoclonal antibodies as well as antibodies generated by SARS-CoV-2 vaccines (1, 2).Hyperimmune anti-SARS-CoV-2 IVIGs (hCoV-2IG) have been manufactured from pooled plasma units of hundred to thousands of convalescent individuals.hCoV-2IG contain immunoglobulin G at a 10-fold higher concentration compared with that in CP, and they are being evaluated for treatment of .To evaluate their therapeutic potential, 19 lots of hCoV-2IG prepared from convalescent individuals infected with SARS-CoV-2 in 2020, prior to circulation of Omicron; 20 IVIG preparations manufactured in 2019 (2019-IVIG) before the COVID-19 pandemic; and 8 IVIG lots manufactured from healthy plasma donations in 2020 (2020-IVIG) were analyzed for neutralization of SARS-CoV-2 Omicron BA.4/BA.5,BA.2.75, BA.2.75.2, BQ.1, BQ.1.1,and XBB subvariants in a pseudovirus neutralization assay (PsVNA) (Supplemental Methods).For comparison, we evaluated 8 CP samples from recovered patients with COVID-19 in early 2020 (2020-CP) and 9 CP samples from Omicron vaccine-breakthrough infections in 2022 (2022-CP).2020-CP showed variable PsVNA50 titers against WA-1, ranging between 10 and 1,343 (geometric mean titer [GMT]: 154), but did not neutralize BQ.1, BQ.1.1,or XBB (Figure 1A and Supplemental Table 2).In contrast, 2022-CP demonstrated robust PsVNA50 titers against WA-1 (GMT: 926) and most neutralized BA.2.75, BA.2.75.2, and BA.4/BA.5 (GMT: 50, 59, and 71, respectively).However, only 4 2022-CP showed low neutralization of BQ.1 (GMT: 25), BQ.1.1 (GMT: 22), and XBB (GMT: 21).As expected, the 2019-IVIG lots did not neutralize any SARS-CoV-2 strain.The 2020-IVIG lots (made from plasma units that were not screened for anti-SARS-CoV-2 neutralizing antibodies) had low PsVNA50 titers against WA-1 (GMT: 35) and did not neutralize Omicron variants (Figure 1A and Supplemental Table 2).The 19 hCoV-2IG lots demonstrated robust neutralization of WA-1 (GMT: 1,615) (Figure 1A).Surprisingly, all 19 lots exhibited neutralization titers against BA.4/BA.5, ranging from 47 to 205 (GMT: 83).Importantly, 15 of the 19 hCoV-2IG lots also neutralized BA.2.75 and BA.2.75.2, with PsVNA50 titers of 22-430 (GMT: 37 and 32, respectively).At least 10 hCoV-2IG lots demonstrated presence of antibodies against BQ.1, BQ.1.1,and XBB subvariants, but the neutralization titers were further reduced (GMT: 21-25; Figure 1A and Supplemental Table 2).Strong correlations